Optimisation of Sub-30 nm Solid Lipid Nanoparticles Loaded With Docetaxel Produced by the Cold-Burst Method: A Particle Size Optimisation Study

Abstract

Introduction: The cold-burst method presents a novel, energy-efficient, and cost-effective approach for solid lipid nanoparticle (SLN) production compared to traditional methods. It involves simple heating and cooling cycles that can create SLNs below 30 nm in size. Given the limitations of conventional docetaxel (DTX) delivery in cancer therapy, SLNs offer a promising solution for improved bioavailability and reduced toxicity. The achievement of sub-30 nm SLNs is particularly significant, as this size range is known to enhance passive tumour targeting via the enhanced permeability and retention (EPR) effect, promote deeper distribution into solid tumours, and improve cellular uptake. This study aimed to optimise the particle size of DTX-loaded SLNs produced via the cold-burst method.

Method: Formulations utilised Compritol 888 ATO (888) and Precirol ATO 5 (ATO5) as lipid components, stabilised by water-soluble (Tween20, BrijS20) and oil-soluble (monoolein) surfactants. A total of 25 SLN formulations were created by systematically varying parameters including type of lipid, type of water-soluble surfactant, DTX concentration (0-5 wt%, equating to 0-5 mg), total surfactant concentration (2-4 wt%), water-soluble surfactant ratio, and number of heating and cooling cycles. Particle size (mean D50) was determined by dynamic light scattering (DLS) using a Malvern Zetasizer Nano ZS series (Malvern Panalytical, Shanghai, China). Statistical comparisons of mean D50 values were performed using one-way analysis of variance (ANOVA) followed by Tukey’s honestly significant difference (HSD) post hoc analysis.

Results: This study’s results consistently demonstrated the successful formation of <30 nm DTX-loaded SLNs for both lipids. Drug loading of up to 5 wt% DTX showed no significant difference in particle size when compared to no drug loading. A significant decrease in particle size was observed with increasing total surfactant concentration (2-4 wt%). Both water-soluble surfactants used in this study, Tween20 and BrijS20, facilitated cold bursting and the creation of sub-30 nm SLNs, with BrijS20 yielding significantly smaller nanoparticles across both lipid types. The most pronounced size reduction for 888 SLNs occurred within the first heating and cooling cycle.

Conclusion: These findings highlight the potential of cold-burst-derived sub-30 nm SLNs as an optimised platform. Our work demonstrates the successful optimisation of particle size for DTX-loaded SLNs, laying a foundation for future comprehensive studies towards enhanced DTX delivery and more effective cancer therapeutics. However, the absence of drug loading quantification, in vitro drug release data, and cellular performance assessments limits the conclusions regarding the therapeutic efficacy of these SLNs.

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Materials And Methods

Lipids To prepare the oil-in-water emulsions, two lipids were used: Precirol ATO 5 (ATO5) and 888. ATO5, purchased from Gattefossé, is a lipid that has been proven to create drug-loaded SLNs [16] and has also been proven to produce SLNs using cold burst [10]. ATO5 consists of glyceryl distearate and glyceryl palmitostearate, which are esters of palmitic (C16) and stearic (C18) acids. 888, purchased from Gattefossé, is a hydrophobic mixture of mono-, di-, and triesters of behenic acid (C22). It has also been shown to successfully create DTX-loaded SLNs [17]. For all SLN formulations, 1 wt% (with respect to 10 g of water, equating to 0.1 g) of either ATO5 or 888 was used. Surfactants To stabilise the emulsions, water-soluble and oil-soluble surfactants were used. For each SLN formulation, the total surfactant concentration ranged between 2 wt% and 4 wt% (with respect to 10 g of water, equating to 0.2-0.4 g). Water-Soluble Surfactants BrijS20 was one of the water-soluble non-ionic surfactants used to stabilise the oil-in-water emulsions. It is mostly used for pharmaceutical applications to improve the solubility of drugs, but research has also shown it can create stable nanoparticles [18]. BrijS20 was purchased from Sigma-Aldrich. Tween20 was the other water-soluble surfactant used to stabilise the oil-in-water emulsions. It is widely used for biochemical applications and has also been shown to create stable SLNs [10]. Tween20 was purchased from Sigma-Aldrich. For each SLN formulation, the ratio of water-soluble surfactant to oil-soluble surfactant ranged from 2:1 to 6:1. This changed the weight of the water-soluble surfactant depending on the total surfactant concentration. The specific weights are detailed later in the Results section.

Optimisation of Sub-30 nm Solid Lipid Nanoparticles Loaded With Docetaxel Produced by the Cold-Burst Method: A Particle Size, Optimisation Study, Oluwaseun Akinniranye, Anastasia Goryanin, Olusegun Akinniranye, DOI: 10.7759/cureus.90291

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